Glucosamine (GlcN) is a naturally occurring amino-sugar that has been used to treat various ailments including osteoarthritis (OA). Animal studies suggest potent anti-inflammatory and disease modifying effects for GlcN. The reported human clinical trials are, however, inconclusive (1-10). In addition, plasma GlcN concentration following effective doses (˜300 mg/kg) (11,12,13) to the rat are several magnitudes greater than those expected or observed following human doses (1500 mg/day) (13). Similarly, GlcN plasma concentrations of products with beneficial effects in the treatment of OA (14), although variable, are substantially higher that those with no or negligible effects (13).
We hypothesized that pro-drugs of GlcN and other amino-sugars such as butyryl glucosamine will possess relatively high bioavailability that yield high concentrations, hence, will be effective against OA and rheumatoid arthritis (RA). Therefore, developing pro-drugs that yield high bioavailability of GlcN or butyryl glucosamine is beneficial.
We attribute the controversial results of various studies to the following points:                (a) GlcN is not a regulated compound, hence, the quality of the available products and also those used in clinical trials are questionable. It has been reported that except for one, all commercially available products contain substantially less GlcN than the label claim (15).        (b) The dosing regimens used are empiric because of scant pharmacologic information. A dose-effect study using a pharmaceutical grade GlcN formulation is lacking. Indeed, clinical trials have typically concentrated on a 1500 mg/day (label claim, very likely <1500 mg/day) regimen. Only animal studies and human trials that have been carried out with relatively high doses or were associated with high plasma GlcN concentrations have reported pharmacological efficacy. GlcN has a low and erratic bioavailability following oral doses, hence, excessively large doses are needed for desired effects.        (c) Due to its physical instability, GlcN is often crystallised along with considerable amount of KCl, hence, a typical tablets containing 500 mg GlcN weighs around 1.4 g. The mere size of the available tablets deters patients from taking these pills more than 500 mg t.i.d. to experience the beneficial effects of higher amount in the body.        